Algeta ASA is gearing up to start pivotal Phase III trials next year of its alpha emitter Alpharadin after reporting two-year Phase II data showing that the drug doubles survival rate over placebo.

The new survival data, presented at the European Conference of Clinical Oncology (ECCO) in Barcelona, Spain, confirms the positive trend seen in the data at 18 months into the 64-patient trial, as published earlier this year in The Lancet. Those results demonstrated that Alpharadin showed a delay in disease progression in patients with hormone-refractory prostate cancer and improved overall survival, with 15 out of 33 patients in the treatment arm still alive at 18 months vs. six of 31 in the placebo group.

At the 24-month follow-up, 10 of the 33 patients (30 percent) in the Alpharadin-treated arm were alive, compared to four of 31 (13 percent) in the placebo arm. Additional data showed that Alpharadin, a bone-seeking radiopharmaceutical based on the alpha particle emitter radium-223, significantly reduced levels of prostate-specific antigen (PSA), and the median time to PSA progression increased from eight weeks to 26 weeks. The drug also appears to have a safety profile that might allow for an extended treatment period to further delay disease progression.

But it is overall survival data that likely will carry more weight with regulators in the long run, as Martinsried, Germany-based GPC Biotech AG and partner Spectrum Pharmaceuticals Inc., of Irvine, Calif., discovered earlier this year, much to the dismay of investors. The companies filed a new drug application for satraplatin, a platinum-based therapy that is aiming for the same hormone-refractory prostate cancer market as Algeta's drug, based on positive progression-free survival data, but opted to withdraw the application in July after an FDA advisory committee recommended waiting for overall survival data, expected around the end of this year. (See BioWorld Today, July 25, 2007.)

Algeta has not yet outlined plans for its Phase III program of Alpharadin, though the Oslo, Norway-based firm said it remains on schedule to begin pivotal studies in 2008. The drug, which is designed to work by accumulating in bone metastases and killing tumor cells by local alpha irradiation, also is being studied in Phase II trials in pain palliation in skeletal metastases from prostate cancer and is in Phase I testing for skeletal metastases in breast cancer.

Founded in 1997 by University of Oslo scientists who discovered the potential of alpha emitters as therapeutic candidates, Algeta has focused its efforts to date primarily on Alpharadin, though it has begun moving earlier stage oncology programs toward the clinic, including a TH-1 targeted therapy that links the alpha emitter thorium-227 to selective antibodies. Algeta raised $29 million in its first venture round in 2005 and added $41 million earlier this year when it went public on the Oslo Stock Exchange.

Shares (OSE:ALGETA) gained NOK1.60 Tuesday to close at NOK41.60 (US$7.55).

In other ECCO news:

• Amgen Inc., of Thousand Oaks, Calif., reported results of a biomarker analysis supporting the use of KRAS as a predictive clinical biomarker for selecting patients who are more likely to respond to treatment with Vectibix (panitumumab) monotherapy. The biomarker analysis of Phase III data met the primary and secondary endpoints by demonstrating that the effect of Vectibix on progression-free survival was confined exclusively to the 60 percent of patients whose tumors harbor normal, non-mutated KRAS, while no effect from Vectibix treatment was observed in patients who had tumors with mutations in KRAS regardless of the endpoint studied. Amgen previously reported results from that study showing that Vectibix monotherapy improved progression-free survival and response rate in heavily pretreated patients with metastatic colorectal cancer after failure of standard chemotherapy. In separate news, Amgen presented data from an Aranesp (darbepoetin alfa) study - the Danish Head and Neck Cancer trial that was stopped late last year due to futility after an interim analysis - showing that patients with squamous-cell carcinoma of the head and neck who were treated with the erythropoiesis-stimulating agent had significantly poorer tumor control after radiotherapy. Of 515 patients eligible for analysis, results demonstrated a poorer outcome with Aranesp treatment in five-year loco-regional control (56 percent with Aranesp vs. 69 percent for the control group), and there were no significant differences in secondary endpoints, including overall survival, the risk of developing distant metastases or in noncancer-related deaths. Aranesp's labeling was updated in March to include the preliminary information from that study. (See BioWorld Today, March 12, 2007.)

• AstraZeneca plc, of London, said results from a 312-patient Phase II EPOC (Endothelin A Proof Of Concept) study of ZD4054 showed no differences in progression-free survival in hormone-resistant prostate cancer, but did show encouraging overall survival data. Patients who received once-daily administration of ZD4054, a specific endothelin A receptor antagonist, had median overall survival of 24.5 months at the 10-mg dose and a median overall survival of 23.5 months at the 15-mg dose, compared to median overall survival of 17.3 months in the placebo group. The company is planning a Phase III program this year consisting of three studies, with the first of those aimed at exploring the efficacy of ZD4054 in metastatic hormone-refractory prostate cancer.

• BioAlliance Pharma SA, of Paris, reported data confirming the efficacy of its antifungal product, miconazole Lauriad, in head and neck cancer patients previously treated with radiotherapy or chemotherapy and suffering from oropharyngeal candidiasis. Results from the 282-patient study showed that the success rate after 14 days of treatment with miconazole Lauriad administered once-daily was not inferior to that of miconazole 500-mg oral gel administered four times per day. A difference of 7.1 percent was observed in favor of the miconazole Lauriad group. The Lauriad mucoadhesive technology is designed to allow an early and prolonged release of therapeutic agents at the site of the disease.

• Merck Serono International SA, of Darmstadt, Germany, reported results from several Erbitux (cetuximab) studies, including the 700-patient CAIRO (2) Phase III trial, which confirmed the drug's safety when added to a combination of capecitabine, oxaliplatin and bevacizumab (Avastin, Genentech Inc.) in first-line metastatic colorectal cancer (mCRC). Data from the Phase III CRYSTAL trial showed a statistically significant increase of progression-free survival in the group receiving Erbitux plus FOLFIRI (an irinotecan-based chemotherapy regimen) compared to the FOLFIRI-alone group, and also showed an overall 15 percent reduction in the risk of mCRC growing or spreading. That study also showed that using Erbitux significantly increased response rate, meaning tumor shrinkage, by 50 percent or more. Merck anticipates using results from the CRYSTAL study as the basis for its application to the European Medicines Agency for extending Erbitux's use as a first-line therapy in mCRC. Merck gained rights to Erbitux outside the U.S. and Canada from New York-based ImClone Systems Inc.

• Ziopharm Oncology Inc., of New York, reported interim Phase II data of ZIO-210 (isophosphoramide mustard) in refractory sarcoma patients showing that 14 of 31 patients (45 percent) have shown a clinically beneficial response, including one partial response, four minor responses and nine with stable disease. In patients with the difficult-to-treat leiomyosarcoma, five of seven patients (71 percent) have stable disease or better with ZIO-210. The trial has enrolled 51 patients to date, and Ziopharm expects to report final data at another scientific meeting later this year. In separate news, the company also presented at the ECCO meeting data from ongoing trials of darinaparsin (ZIO-101) in advanced hematological malignancies. As a measure of clinical activity, five of 12 acute myelogenous leukemia patients (42 percent) had a decrease in peripheral blood myeloblasts, while the two patients with myelodysplasia experienced stable disease. Darinaparsin, a small-molecule organic arsenic compound, also was found to be well tolerated, and adverse events were mild to moderate in intensity.

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